Acquired antibody to factor XI in a patient with congenital factor XI deficiency.
Acquired antibody to factor XI in a patient with congenital factor XI deficiency.
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先天性 XI 因子缺乏症患者获得了 XI 因子抗体。
DOI：
10.1172/jci110566
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Owen,J
中科院分区：
文献类型：
--
作者：
Stern,DM;Nossel,HL;Owen,J
研究的结果，在患者先天性缺乏因子十一谁开发抑制剂提出。患者表现为严重的、明显的自发性大腿出血，尽管输注了新鲜冷冻血浆，但出血仍在继续，但对激活的凝血酶原复合物反应迅速。在血浆治疗期间，他的凝血时间和因子XI水平无反应，因子XI抑制剂滴度达到6,000 U/ml。该抑制剂为多克隆免疫球蛋白G (IgG)，主要为4亚类。通过分离的抑制剂与聚丙烯酰胺珠结合，能够选择性地从正常血浆中去除因子XI，证明了抗体对因子XI的特异性。研究了125i标记因子XI与抑制剂的结合，发现其亲和常数为1.65 × 1010l /mol。抗体与因子XI的络合被证明可以阻断凝血因子的多种活性。与抗体络合的因子XI不与高分子量激肽原结合，也不被双链因子XII激活和切割。活化因子XI与抑制剂的复合体阻止了因子IX的裂解和活化。因此，抑制剂似乎通过结合因子XI分子上的多个位点并阻止其与其他分子相互作用而起作用。临床上这些抑制剂与因子XI的相互作用导致严重的因子XI缺乏状态。该病例的临床情况是，严重出血对血浆输注难治，但对另一种促凝剂有反应，这表明内在系统激活的缺陷是关键，支持因子XI确实参与正常止血的推断。该患者的临床病程，在抑制剂存在的情况下只有两次出血记录，不像严重因子VIII或IX缺乏症患者那样严重。这表明，因子XI和因子IX的生理激活并不仅仅是一系列的，因为因子XII、XI、VIII和IX的缺乏应该会产生类似的止血后果。我们认为XII和XI旁路的独立机制在凝血的生理激活中很重要。
The results of studies in a patient with congenital deficiency of Factor XI who developed an inhibitor are presented. The patient presented with a severe, apparently spontaneous bleed into the thigh, which progressed despite infusion of fresh frozen plasma, but which responded promptly to activated prothrombin complex. During therapy with plasma his clotting time and Factor XI level were unresponsive and a Factor XI inhibitor titer of 6,000 U/ml was attained. The inhibitor was isolated and found to be polyclonal immunoglobulin G (IgG), predominantly of subclass 4. The specificity of the antibodies for Factor XI was shown by the ability of isolated inhibitor bound to polyacrylamide beads to remove Factor XI selectively from normal plasma. The binding of125I-labeled factor XI to the inhibitor was studied and an affinity constant of 1.65 × 1010liter/mol was found. Complexing of the antibodies with Factor XI was shown to block multiple activities of the clotting factor. Factor XI complexed with antibody did not bind to high molecular weight kininogen or undergo activation and cleavage by two-chain Factor XII. The complex of activated Factor XI with inhibitor prevented the cleavage and activation of Factor IX. Hence the inhibitor appears to act by binding to multiple sites on the Factor XI molecule and preventing its interaction with other molecules. Clinically these interactions of the inhibitor with Factor XI result in a state of severe Factor XI deficiency.The clinical circumstances of the case, with severe hemorrhage refractory to plasma infusion but readily responsive to an alternate clot-promoting agent, suggest that a defect of intrinsic system activation was critical, supporting the inference that Factor XI does participate in normal hemostasis. The clinical course of this patient, who has only had two documented hemorrhages in the presence of the inhibitor, is not as severe as that of patients with severe Factor VIII or IX deficiency. This suggests that physiologic activation of Factors XI and IX does not occur exclusively in series because deficiency of factors XII, XI, VIII, and IX should then have similar hemostatic consequences. We propose that independent mechanisms for bypass of Factors XII and XI are important in physiologic activation of coagulation.